Accelerated Wound Border Closure Using a Microemulsion Containing Non-Inhibitory Recombinant α1-Antitrypsin
Wound healing requires a non-compromising combination of inflammatory and anti-inflammatory processes. Human α1-antitrypsin (hAAT), a circulating glycoprotein that rises during acute-phase responses and during healthy pregnancies, is tissue-protective and tolerance-inducing; although anti-inflammato...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/7364 |
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| author | Alon Gimmon Lior Sherker Lena Kojukarov Melodie Zaknoun Yotam Lior Tova Fadel Ronen Schuster Eli C. Lewis Eldad Silberstein |
| author_facet | Alon Gimmon Lior Sherker Lena Kojukarov Melodie Zaknoun Yotam Lior Tova Fadel Ronen Schuster Eli C. Lewis Eldad Silberstein |
| author_sort | Alon Gimmon |
| collection | DOAJ |
| description | Wound healing requires a non-compromising combination of inflammatory and anti-inflammatory processes. Human α1-antitrypsin (hAAT), a circulating glycoprotein that rises during acute-phase responses and during healthy pregnancies, is tissue-protective and tolerance-inducing; although anti-inflammatory, hAAT enhances revascularization. hAAT blocks tissue-degrading enzymes, including neutrophil elastase; it is, therefore, unclear how wound healing might improve under hAAT-rich conditions. Here, wound healing was examined in the presence of recombinant hAAT (hAAT<sup>WT</sup>) and protease-inhibition-lacking hAAT (hAAT<sup>CP</sup>). The impact of both hAAT forms was determined by an epithelial cell gap closure assay, and by excisional skin injuries via a microemulsion optimized for open wounds. Neutrophilic infiltration was examined after 8 h. According to results, both hAAT forms accelerated epithelial gap closure and excisional wound closure, particularly at early time points. Unlike dexamethasone-treated wounds, both resulted in closed borders at the 8-h time point. In untreated and hAAT<sup>CP</sup>-treated wounds, leukocytic infiltrates were widespread, in hAAT<sup>WT</sup>-treated wounds compartmentalized and in dexamethasone-treated wounds, scarce. Both hAAT forms decreased interleukin-1β and increased VEGF gene expression. In conclusion hAAT improves epithelial cell migration and outcomes of in vivo wounds irrespective of protease inhibition. While both forms of hAAT allow neutrophils to infiltrate, only native hAAT created discrete neutrophilic tissue clusters. |
| first_indexed | 2024-03-09T21:47:59Z |
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| id | doaj.art-6e0d41351a664ed0a8517c5dadd8b8d0 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:47:59Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6e0d41351a664ed0a8517c5dadd8b8d02023-11-23T20:12:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012313736410.3390/ijms23137364Accelerated Wound Border Closure Using a Microemulsion Containing Non-Inhibitory Recombinant α1-AntitrypsinAlon Gimmon0Lior Sherker1Lena Kojukarov2Melodie Zaknoun3Yotam Lior4Tova Fadel5Ronen Schuster6Eli C. Lewis7Eldad Silberstein8Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, IsraelDepartment of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, IsraelDepartment of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, IsraelDepartment of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, IsraelDepartment of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, IsraelDepartment of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, IsraelDepartment of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, IsraelDepartment of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, IsraelDepartment of Plastic and Reconstructive Surgery, Soroka University Medical Center, Beer-Sheva 8410101, IsraelWound healing requires a non-compromising combination of inflammatory and anti-inflammatory processes. Human α1-antitrypsin (hAAT), a circulating glycoprotein that rises during acute-phase responses and during healthy pregnancies, is tissue-protective and tolerance-inducing; although anti-inflammatory, hAAT enhances revascularization. hAAT blocks tissue-degrading enzymes, including neutrophil elastase; it is, therefore, unclear how wound healing might improve under hAAT-rich conditions. Here, wound healing was examined in the presence of recombinant hAAT (hAAT<sup>WT</sup>) and protease-inhibition-lacking hAAT (hAAT<sup>CP</sup>). The impact of both hAAT forms was determined by an epithelial cell gap closure assay, and by excisional skin injuries via a microemulsion optimized for open wounds. Neutrophilic infiltration was examined after 8 h. According to results, both hAAT forms accelerated epithelial gap closure and excisional wound closure, particularly at early time points. Unlike dexamethasone-treated wounds, both resulted in closed borders at the 8-h time point. In untreated and hAAT<sup>CP</sup>-treated wounds, leukocytic infiltrates were widespread, in hAAT<sup>WT</sup>-treated wounds compartmentalized and in dexamethasone-treated wounds, scarce. Both hAAT forms decreased interleukin-1β and increased VEGF gene expression. In conclusion hAAT improves epithelial cell migration and outcomes of in vivo wounds irrespective of protease inhibition. While both forms of hAAT allow neutrophils to infiltrate, only native hAAT created discrete neutrophilic tissue clusters.https://www.mdpi.com/1422-0067/23/13/7364corticosteroidsinfiltrationinflammationdirected mutationneutrophilsVEGF |
| spellingShingle | Alon Gimmon Lior Sherker Lena Kojukarov Melodie Zaknoun Yotam Lior Tova Fadel Ronen Schuster Eli C. Lewis Eldad Silberstein Accelerated Wound Border Closure Using a Microemulsion Containing Non-Inhibitory Recombinant α1-Antitrypsin International Journal of Molecular Sciences corticosteroids infiltration inflammation directed mutation neutrophils VEGF |
| title | Accelerated Wound Border Closure Using a Microemulsion Containing Non-Inhibitory Recombinant α1-Antitrypsin |
| title_full | Accelerated Wound Border Closure Using a Microemulsion Containing Non-Inhibitory Recombinant α1-Antitrypsin |
| title_fullStr | Accelerated Wound Border Closure Using a Microemulsion Containing Non-Inhibitory Recombinant α1-Antitrypsin |
| title_full_unstemmed | Accelerated Wound Border Closure Using a Microemulsion Containing Non-Inhibitory Recombinant α1-Antitrypsin |
| title_short | Accelerated Wound Border Closure Using a Microemulsion Containing Non-Inhibitory Recombinant α1-Antitrypsin |
| title_sort | accelerated wound border closure using a microemulsion containing non inhibitory recombinant α1 antitrypsin |
| topic | corticosteroids infiltration inflammation directed mutation neutrophils VEGF |
| url | https://www.mdpi.com/1422-0067/23/13/7364 |
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